Do clinical trials reflect reality?

Renal transplant recipients and donors are becoming increasingly more marginal, with more expanded criteria (ECD) and donation after circulatory death (DCD) donors and increasingly older recipients with multiple comorbidities. Despite this, high-risk donors and recipients are often excluded from clinical trials, leading to uncertainty about the generalizability of findings.

In order to highlight the extent of this problem in renal transplantation, the CET has recently published a systematic review of inclusion/exclusion criteria in trials of renal transplant immunosuppression. Immunosuppression trials make up over half of the RCTs published in the field. We analysed the inclusion/exclusion criteria in 174 trials published between 2010 and 2014, and found significant differences between the populations included in clinical trials and those in the general transplant population.  In particular, nearly 25% studies excluded DCD donor kidneys, despite these making up over 30% adult kidney transplants in the UK.  38% of trials reported an upper age limit for recipient inclusion, despite an increasingly ageing wait-list population: 22% of the kidney USA waiting list are aged over 65, and 31% of the UK waiting list are over the age of 60. High immunological risk recipients are also commonly excluded, with over 20% studies excluding patients with a previous transplant, a population that makes up 24% of the UK waiting list. Sensitised patients are often excluded from participating in trials, despite 30% of US transplant recipients having a PRA >20% at the time of transplant.

The study also found significant discrepancies between inclusion/exclusion criteria defined in trial protocols (from registries) and those reported in the final manuscript. This raises the real possibly of selection bias resulting from changing criteria during the conduct of a trial.

Our findings suggest many recent immunosuppression trials have restrictive inclusion criteria which may not be reflective of current renal transplant populations. Caution is advised when applying the results of these studies to excluded populations, and researchers are encouraged to consider inclusion of these groups in future studies so that the safety and efficacy of interventions in these populations can be confirmed.

To read the full paper, head over to the Transplant International website.